FACE TO FACEResearch Scientist, Environmental Trace Substances Laboratory, Center for Environmental Science and Technology, University of Missouri, Rolla
More than 200,000 joint replacements are implanted every year in the United States. Most of these, especially artificial hips and knees, are placed in the elderly whose sedentary lifestyles minimize wear. For many of these patients, long-term effects of the implants are of little concern. But as shoulder, elbow, knee, and even hip implants are increasingly placed into younger patients, the effects that the implants may have 20 to 30 years down the road become important. For these patients, the wear and tear that may cause metal to shed from implants into the bloodstream, and the corrosion of materials that are in contact with body fluids are a concern. And while some of the elements used in artificial joints are known carcinogens at high levels, the long-term effects of low doses are unknown. Such concerns and long-term effects need to be addressed, however, and Lijian Yu, a research scientist at the Environmental Trace Substances Laboratory (ETSL) at the University of Missouri in Rolla, is working with other researchers to do just that.
As part of a five-year $750,000 grant from the National Institutes of Health, Yu is cooperating with researchers at Rush PresbyterianSt. Luke's Medical Center in Chicago who are documenting the wear seen in implants and then sending biological samples to ETSL. In this research, Yu will investigate what happens to the primary metalsaluminum, titanium, vanadium, cobalt, chromium, and nickelused in artificial joints following implantation. He and his colleagues will also try to determine how these metals spread to other sites in the body. In this interview with MD&DI, Yu describes the study, the technology behind it, and how its results could affect the development of implants.
What is the relationship between Rush PresbyterianSt. Luke's Medical Center and your laboratory?
The research project begins at Rush PresbyterianSt. Luke's, where they are looking at systemic implications of total joint replacements. One of the researchers there, Jorge Galante, designed a lot of these total joint implants. Another is the principal investigator, Joshua Jacobs, who directs and coordinates the whole project. According to their experiences, these metal implants in the human body are very successful because the devices are usually used in people of advanced age. These devices help a lot of people who otherwise would not be able to walk or function normally.
With the success of these devices in older people, those in the industry and the medical field are wondering whether such devices can be supplied to younger patients. The objective is to develop better designs for total joint implants for use in older people as well as in younger people. We'd also like to determine whether corrosion of these implants, which cannot be avoided, will have a long-term effect on a human being. Perhaps by controlling some design components of the implant, it may be possible to reduce the amounts of trace metals deposited in the body.
So design is an important consideration in your work, because one design might cause more or less wear of the materials than another?
Yes. We'll be analyzing urine serum, as well as tissues, from these patients. These will indicate whether corrosion takes place. If there's corrosion, you would expect the corroded product to bind to the tissue, or to dissolve into body fluids carried around with blood or urine. My part in this research is to point out the extent of corrosion that has occurred. This may shed light on the role a specific design has played in corrosion.
What's the current status of the project?
We've just begun. We have not yet analyzed any samples from patients, but we have developed a method to study the very low amounts of aluminum, titanium, and other metals in serum using trace metal techniques. The problem is that these techniquessuch as graphite furnace, atomic absorption, spectrometry, or neutron activationneed a pretreatment of a sample such as separation or preconcentration to eliminate interferences. And sometimes the sensitivity of the technique is not enough to detect the extremely low amounts of these elements inside the human body.
We're using the latest technology, which is called electrothermal vaporization inductively coupled plasma mass spectrometry (ICPMS). Basically, it vaporizes the sample with these elements into a high-temperature stream, and then a stream of gas carries these elements into a plasma at a temperature of about 6000°C. This high-temperature source basically ionizes everything, and these ions are then sent to a mass spectrometer where they are detected.
Where was this technology developed?
The basic technology was developed in the 1980s by groups in England, Canada, and the United States. From this, several sample introduction technologies have been developed. Electrothermal vaporization sample introduction technology is one of these.
What is meant by sample introduction technology?
ICPMS basically requires a dilute aqueous samplea homogeneous type of sample. But the body fluid from human beings does not aspirate very well. It is thick and does not become an aerosol very readily. So in order to get the sample into the detector, it somehow needs to be transported into this high-temperature plasma source, and that's where the electrothermal vaporization comes into play.
In addition to using a lot of off-the-shelf technology, will you also have to develop modifications?
The next step will probably need this kind of work. Currently, we're just using the stock techniques that are available but we have to develop a method ourselves.
Where are you in terms of developing this method?
We have developed a methodology for the serum analysis. This took a long time because there are a lot of technical difficulties in analyzing the metal elements in serum, because the serum contains calcium, chlorine, and phosphorus, as well as carbon. These interfere with the analysis of aluminum, titanium, and vanadium. We have to devise ways to alleviate these interferences before any measurements can be done. The method has to be very stable because these samples are collected over a long period of timesay, five to seven yearsand the analytical data collected during this period should be comparable to those collected seven years later in order to establish a clear trend as to whether or not the device works.
How are the laboratory data correlated to the clinical data?
Rush Medical Center is designing a statistical model for how these samples are collected during a specific period from certain numbers of patients. They will then send these samples to us, and we will analyze them here. These data will be collated in terms of numbers of patients as well as the period over which these data were collected, and then we'll come to a conclusion as to whether there is an effect.
So you will be looking for patterns that develop over the next seven years?
Rush Medical Center has a large library of samples collected from the patients over the years, so we may not need to wait seven years to get the desired samples. But in any case, we will be looking at increasing or decreasing concentrations of these particular metals over time.
You said you're looking at aluminum, titanium, vanadium, cobalt, chromium, and nickel. Is that a comprehensive list, or might you be looking at other metals?
Those are the basic metals because there are really only two types of alloys used in this industry. One is the titanium alloy, which is made up of titanium, aluminum, and vanadium; the other is a stainless- steel-based alloy, which is chromium, nickel, and cobalt.
When do you expect to start seeing results from this study?
Hopefully, we'll have some results in a year. We are currently at the stage of developing the methodologyand we're trying to develop all the methods at the same time so that these methods can be used by other laboratories and can provide the basis for similar research elsewhere.